Theranostics 2020; 10(11):4958-4966. doi:10.7150/thno.42121 This issue

Research Paper

Imaging of tumor colonization by Escherichia coli using 18F-FDS PET

Sae-Ryung Kang1,2, Eui Jeong Jo2, Vu Hong Nguyen1,3, Ying Zhang2, Hee Seung Yoon2, Ayoung Pyo2, Dong-Yeon Kim1,2, Yeongjin Hong4, Hee-Seung Bom1,2, Jung-Joon Min1,2✉

1. Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Jeonnam, Korea
2. Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Hwasun, Jeonnam, Korea
3. Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
4. Department of Microbiology, Chonnam National University Medical School, Hwasun, Jeonnam, Korea

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Kang SR, Jo EJ, Nguyen VH, Zhang Y, Yoon HS, Pyo A, Kim DY, Hong Y, Bom HS, Min JJ. Imaging of tumor colonization by Escherichia coli using 18F-FDS PET. Theranostics 2020; 10(11):4958-4966. doi:10.7150/thno.42121. Available from https://www.thno.org/v10p4958.htm

File import instruction

Abstract

Graphic abstract

Tumor-targeting bacteria have been actively investigated as a new therapeutic tool for solid tumors. However, in vivo imaging of tumor-targeting bacteria has not been fully established. 18F-fluorodeoxysorbitol (FDS) positron emission tomography (PET) is known to be capable of imaging Gram-negative Enterobacteriaceae infection. In the present study, we aimed to validate the use of 18F-FDS PET for visualization of the colonization and proliferation of tumor-targeting Escherichia coli (E. coli) MG1655 in mouse tumor models.

Methods: E. coli (5 × 107 colony forming unit) were injected intravenously into BALB/c mice bearing mouse colon cancer (CT26). Before and 1, 3, and 5 days after the bacterial injection, PET imaging was performed following i.v. injection of approximately 7.4 MBq of 18F-FDS. Regions of interest were drawn in the engrafted tumor and normal organs including the heart, liver, lung, brain, muscle, and intestine. Semiquantitative analysis was performed using maximum standardized uptake value (SUVmax).

Results: 18F-FDS uptake was significantly higher in tumors colonized by live E. coli MG1655 than in uncolonized tumors (p < 0.001). The PET signals in the colonized tumors at 3 days after bacterial injection were 3.1-fold higher than those in the uncolonized tumors. Tumoral 18F-FDS uptake correlated very strongly with the number of E. coli in tumors (r = 0.823, p < 0.0001). Cross sectional analysis of autoradiography, bioluminescence, and pathology revealed that the 18F-FDS uptake sites in tumors matched the locations of E. coli MG1655.

Conclusion: In conclusion, 18F-FDS PET is expected to be useful for the semiquantitative visualization of tumor-targeting bacteria when bacterial cancer therapy is performed using Gram-negative Enterobacteriaceae such as E. coli.

Keywords: tumor-targeting bacteria, Escherichia coli, bacterial cancer therapy, 18F-fluorodeoxysorbitol (18F-FDS), positron emission tomography (PET)